Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells.

Abstract

Prostaglandin H (PGH) synthase (EC (6)(7)(8). However, earlier in vivo studies raised questions whether the pharmacologic activity of aspirin and other nonsteroidal antiinflammatory drugs is entirely mediated through this mechanism (1, 9). PGH synthase has been found to have a rapid turnover rate (half-life of 5-6 min) in the few tissues examined (10, 11). Cytokines and phorbol diesters are known to induce synthesis of the enzyme, thereby raising the level of PGH synthase protein severalfold over the basal levels (11)(12)(13)(14). In this communication, we report results of studies with cultured endothelial cells that indicate that aspirin and salicylate are able to inhibit the de novo synthesis of the enzyme by action at the level of gene expression.

Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate

“…The media were collected, and prostaglandin E 2 (PGE 2 ) was measured by a highly specific enzymeimmunoassay. The COX activity was analyzed further by reverse-phase HPLC as described (7). In brief, cells were treated with [1-14 C] arachidonic acid at 37°C for 10 min.…”

“…Salicylic acid has been a known NSAID for over a century, but its mechanism of action remains a pharmacological enigma. It has virtually no inhibitory activity against purified COX-1 or COX-2, although it inhibits prostaglandin synthesis in intact cells (7). To elucidate the mechanism by which salicylic acid exerts its antiinflammatory action, we evaluated the effects of aspirin and sodium salicylate on COX-2 expression in human umbilical vein endothelial cells (HUVEC) and human foreskin fibroblasts (HFF) induced by inflammatory mediators.…”

On Radiation Damage to Normal Tissues and its Treatment: II. Anti-inflammatory drugs

“…Although the role of growth factors ( I ) and eicosanoids (the present paper) in the development and treatment of radiation reactions has been discussed separately, the two chemically disparate families of diffusible mediators are closely linked ( 11 2, 146, 152, 154-157, 160, 161, 165, 167,170,182,183,266,[294][295][296][297].…”

“…A few NSAID can also inhibit PLA, activity (180,181). Their hindrance of PGH synthase expression is a matter of current debate (169,182,183). Some of the anti-inflammatory actions of NSAID do not involve interference with the generation of eicosanoids (184)(185)(186)(187)(188)(189)(190).…”

Aspirin inhibits endothelial cell activation induced by antiphospholipid antibodies

“…Drugs which block the activity of inflammatory cytokines might therefore affect the EC response to APLA. One such drug, aspirin, inhibits the activation of EC by TNF-a or IL-1 [12][13][14][15][16]. Alone, or in conjunction with anticoagulants, this drug is already used for the antithrombotic treatment of patients with APS [17][18][19][20].…”